• Carina Iskander, David Z Cherney, Kristin K Clemens, Stephanie N Dixon, Ziv Harel, Nivethika Jeyakumar, Eric McArthur, Flory Tsobo Muanda, Chirag R Parikh, J Michael Paterson, Navdeep Tangri, Jacob A Udell, Ron Wald, and Amit X Garg.
• Departments of Epidemiology and Biostatistics (Iskander, Clemens, Dixon, Jeyakumar, Muanda, Garg), and Medicine (Clemens, Garg), Western University, London, Ont.; Department of Medicine, Division of Nephrology (Cherney), Toronto General Hospital, University of Toronto; Department of Physiology, and Banting and Best Diabetes Centre (Cherney), University of Toronto; Division of Nephrology (Harel, Wald), St. Michael's Hospital; Faculty of Medicine (Udell), University of Toronto; Cardiovascular Division (Udell), Department of Medicine and Women's College Research Institute, Women's College Hospital, Toronto, Ont.; Toronto, Ont.; ICES (Clemens, Dixon, Jeyakumar, McArthur, Muanda, Paterson, Garg), London, Ont.; Division of Nephrology (Parikh), School of Medicine, Johns Hopkins University, Baltimore, Md.; Department of Internal Medicine (Tangri), Max Rady College of Medicine, University of Manitoba; Seven Oaks General Hospital (Tangri), Chronic Disease Innovation Centre, Winnipeg, Man. carina.iskander@ices.on.ca.
• CMAJ. 2020 Apr 6; 192 (14): E351E360E351-E360.

BackgroundRegulatory agencies warn about the risk of acute kidney injury (AKI) after the initiation of sodium-glucose cotransporter-2 (SGLT2) inhibitors. Our objective was to quantify the 90-day risk of AKI in older adults after initiation of SGLT2 inhibitors in routine clinical practice.MethodsWe conducted a population-based retrospective cohort study in Ontario, Canada, involving adults with diabetes who were aged 66 years or older and who were newly dispensed either an SGLT2 inhibitor or a dipeptidyl peptidase-4 (DPP4) inhibitor in an outpatient setting between 2015 and 2017. We used inverse probability of treatment weighting based on a propensity score to balance the 2 groups on measured baseline characteristics. The primary outcome was 90-day risk of a hospital encounter (i.e., visit to the emergency department or admission to hospital) with AKI, which we defined by a 50% or greater increase in the concentration of serum creatinine from the baseline value or an absolute increase of at least 27 μmol/L after an SGLT2 or DDP4 inhibitor was dispensed. We obtained weighted risk ratios using modified Poisson regression and weighted risk differences using binomial regression.ResultsWe included 39 094 patients with a median age of 70 (interquartile range 68-74) years in the study. Relative to new use of a DPP4 inhibitor, initiation of a SGLT2 inhibitor was associated with a lower 90-day risk of a hospital encounter with AKI: 216 events in 19 611 patients (1.10%) versus 388 events in 19 483 patients (1.99%); weighted risk ratio 0.79 (95% confidence interval 0.64-0.98).InterpretationIn routine care of older adults, new use of SGLT2 inhibitors compared with use of DPP4 inhibitors was associated with a lower risk of AKI. Together with previous evidence, our findings suggest that regulatory warnings about AKI risk with SGLT2 inhibitors are unwarranted.© 2020 Joule Inc. or its licensors.

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